Actinic Keratoses: New Approaches to Treatment

Mark Lebwohl, MD, presented the session “Actinic Keratosis: Optimizing the Use of Topical Treatment Options in Clinical Practice” on the second day of Fall Dermatology Week 2022, beginning the discussion with patients with actinic keratosis in sun-exposed areas, numerous cancerous and precancerous skin lesions with multiple actinic keratosis, and cutaneous horn.

Dr Lebwohl mentioned that actinic keratosis is very common: “Actinic keratosis represent the most common dermatologic diagnosis in patients 45 years of age and older in the United States.”

Actinic keratosis should be prevented to stop its development to squamous cell carcinoma. As Dr Lebwohl emphasized, “72% of cutaneous cell carcinomas arise in actinic keratosis.” He drove the point home and informed, “Metastatic cutaneous squamous cell carcinoma derives from actinic keratosis.” In a study of 1689 patients aged 40 years and older seen on 2 consecutive years over a 5-year period, there were 21,905 keratoses present at the first visit. The results of the study included:

• Over 12 months, 28 squamous cell carcinomas developed
• 60% developed from clinical actinic keratosis
• 40% developed from normal skin
• Risk estimated to be less than 1 per 1000 per year

In another study, the risk of progression to invasive disease was estimated as ranging from .025% to 16%.

Next, Dr Lebwohl elaborated on the steps of progression of actinic keratosis to squamous cell carcinoma, “You start out with asymptomatic actinic keratosis, it becomes an inflamed actinic keratosis, which then becomes a squamous cell carcinoma. So, there is a stepwise loss of differentiation.”

Dr Lebwohl moved toward the scientific basis of skin cancer and mentioned, “UV mutates the tumor suppression gene p53. Mutated cells clonally expand and lead to the development of actinic keratosis.”

“Cryotherapy still remains the leading treatment for actinic keratosis,” stated Dr Lebwohl, in terms of larger treatment areas. He also briefly mentioned other treatment options, including, “5-fluorouracil, imiquimod, and ingenol mebutate (no longer on the market).” Cryosurgery is commonly used for cutaneous lesions. However, this procedure can leave white spots and there is a large reoccurrence rate.

In a random trial of 4 treatment approaches for actinic keratosis, there were several flaws, including that it was unblinded, different treatment regimens were used, and adverse events were downplayed.

In another study of treating actinic keratosis with 0.5% fluorouracil cream for 1, 2, or 4 weeks, ““Patients treated for 1 week experienced significant improvements compared with [the] vehicle, although efficacy increased with increasing treatment duration. Most patients experienced mild to moderate facial irritation of predictable onset and duration.”

Dr Lebwohl gave insights into the complete clearance rates with imiquimod from combined 2 times per week studies, and imiquimod rated at 45.1%, whereas the vehicle was 3.2%.

Dr Lebwohl moved on to ingenol mebutate gel as a treatment, pointing out that “ingenol mebutate gel induces an actinic keratosis site reaction and a transient local skin response in the whole field treated.”

He also touched on tirbanibulin, which can be used instead of ingenol mebutate. Tribanibulin works by a novel mechanism of action and is a potent nonpeptide, nonATP, competitive tubulin polymerization and Src kinase inhibitor. Tirbanibulin is US Food and Drug Administration approved to treat periungual squamous cell carcinoma.

To conclude, Dr Lebwohl discussed the cost of tirbanibulin, “The average price is $1191.24.” He recommended, “to check individual pharmacies to find out what the actual cost is.”

Reference
Lebwohl M. Actinic keratosis: optimizing the use of topical treatment options in clinical practice. Presented at: Dermatology Week 2022; September 14-17, 2022; Virtual.